TIM-4 Expressed on APCs Induces T Cell Expansion and Survival

Year: 2008

Type: article

Abstract: TIM (T cell, Ig, mucin) proteins can regulate T cell immune responses. Tim-4 mRNA is not expressed in T cells, but exclusively in APCs. Tim-4 is a ligand for Tim-1 and Tim-4.Ig fusion protein was shown to either inhibit or expand T cells. However, the molecular basis for such opposite effects was not defined. By generating mAbs, we show that expression of Tim-4 protein is restricted to CD11c(+) and CD11b(+) cells and is up-regulated upon activation. We show that Tim-4 specifically phosphorylates Tim-1 and induces T cell expansion by enhancing cell division and reducing apoptosis. Tim-4 also induces the phosphorylation of signaling molecules LAT, Akt, and ERK1/2 in T cells. Tim-4, expressed on APCs, is a costimulatory molecule that promotes T cell expansion and survival by cross-linking Tim-1 on T cells.

Source: The Journal of Immunology

DOI: 10.4049/jimmunol.180.7.4706

Authors: Roselynn Rodriguez-Manzanet, Jennifer Hartt Meyers, Savithri Balasubramanian, Jacqueline Slavik, Nasim Kassam, Valerie Dardalhon, Edward A Greenfield, Ana C Anderson, Raymond A Sobel, David A Hafler, Terry B Strom, Vijay K Kuchroo

Institutions: Brigham and Women's Hospital, Harvard University, Beth Israel Deaconess Medical Center, VA Palo Alto Health Care System, Veterans Health Administration, Stanford Medicine, Stanford University

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Multiple Sclerosis Society, Multiple Sclerosis Society, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke

OpenAlex ID: W1558405203